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VMNS2e is a novel biphenyl compound, which in previous studies had showed most favourable interactions with the active site of protein tyrosine phosphatase 1B (PTP1B). The effect of acute and chronic treatment of VMNS2e (30mg/kg) was investigated in ob/ob mice. Plasma glucose was measured after acute administration of VMNS2e (30mg/kg) in both lean and ob/ob mice. In the chronic study, VMNS2e (30mg/kg) was given orally, once daily for 60days. Metformin (300mg/kg) was taken as standard therapy. Body weight, food intake and blood glucose was measured weekly while glycosylated hemoglobin A(1c) (HbA(1c)), insulin, triglyceride, total cholesterol, low density lipoprotein (LDL), fructosamine, non esterified fatty acid and organ weight were estimated after the completion of treatment period. Oral glucose tolerance test was performed on the last day of treatment. Liver and epididymal fat weights were taken. Acute dose of VMNS2e elicited an anti hyperglycemic effect. It reduced blood glucose by 14% (0.5h) and 35.6% (6h). Chronic VMNS2e treatment improved glucose tolerance by 25.3%. It decreased blood glucose levels. Hyperinsulinemia was reduced (19.6%). VMNS2e treatment had no significant effect on body weight and food consumption. VMNS2e treatment exhibited significant reduction (28.2%) in HbA(1c), plasma triglyceride (49%), LDL (24%) and fructosamine (13%) levels. VMNS2e treatment did not alter total cholesterol and non esterified fatty acid levels. Epididymal fat/body weight ratio was reduced (26.3%). VMNS2e exhibited both acute and chronic anti hyperglycemic effect, insulin sensitivity along with improvement in various lipid parameters and glycemic control., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Aim: To study the effect of a new biphenyl synthetic compound showing interactions with the active site of protein tyrosine phosphatase 1B by docking and molecular dynamics, VMNS2e in streptozotocin-induced diabetic nephropathy in rats with various renal function parameters and renal ultrastructure., Methods: Streptozotocin (55 mg/kg)-induced diabetic rats were orally treated once daily with VMNS2e (30, 60, and 120 mg/kg) for 8 weeks. The body weight and blood glucose levels of the rats were recorded during the study period. After 8 weeks of treatment creatinine clearance, urinary protein, blood urea nitrogen, urinary albumin excretion rate, and insulin levels were measured. An ultrastructure study of the kidney tissue was performed and the glomerular basement membrane thickness was measured., Results: Eight weeks of VMNS2e treatment significantly reduced the fasting blood glucose level, attenuated elevating blood urea nitrogen levels, and reduced glomerular basement membrane thickness., Conclusion: It is concluded that VMNS2e treatment at 30 and 60 mg/kg, when given for 8 weeks, partly ameliorated early diabetic nephropathy in diabetic rats., (© 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.)

The aim of the present investigation was to evaluate the antidiabetic activity of cycloart-23-ene-3beta, 25-diol (called as B2) isolated from stem bark of Pongamia pinnata in streptozotocin-nicotinamide induced diabetic mice. Diabetes was induced in mice by injecting streptozotocin (200mg/kg, i.p.) after 15 min nicotinamide (110 mg/kg, i.p.). The mice were divided into following groups; I - nondiabeteic, II - diabetic control, III - glybenclamide (10mg/kg, p.o.), IV - B2 (1mg/kg, p.o.) and V - B2 (3mg/kg, p.o., only for acute study). Serum glucose was determined periodically. Body weight, food and water intake were recorded daily. Oral glucose tolerance test was performed on day 28. Biochemical and enzyme antioxidant parameters were determined. Histology of pancreas was performed. B2 and glybenclamide treatment reduced serum glucose in acute study. However in chronic study, increase in body weight and decrease in food and water intake was observed. Increased glucose utilization was observed in oral glucose tolerance test. Both glybenclamide and B2 increased serum and pancreatic insulin. Glycosylated haemoglobin, serum cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, globulin, bilirubin, lactate dehydrogenase, urea and uric acid were decreased significantly after B2 treatment. B2 treatment decreased liver malondialdehyde but increased superoxidase dismutase and reduced glutathione. Histologically, focal necrosis was observed in the diabetic mouse pancreata but was less obvious in treated groups. The mechanism of B2 appears to be due to increased pancreatic insulin secretion and antioxidant activity., (2010 Elsevier B.V. All rights reserved.)

Aim of the Study: The aim of the study was to evaluate the antihyperglycaemic activity of aqueous (PPSB-AQE) and petroleum ether (PPSB-PEE) extract of stem bark Pongamia pinnata in alloxan induced diabetic mice., Materials and Methods: Diabetes was induced in mice by alloxan (80 mg/kg, i.v.). After acute and subacute treatment serum glucose was determined. OGTT was performed in PPSB-PEE pretreated animals., Results: PPSB-PEE (25, 50, 100, 200 and 400mg/kg) showed significant reduction in serum glucose level in acute and subacute studies. The antihyperglycaemic effects of PPSBPE (100, 200 and 400mg/kg) showed onset at 2h and peak effect at 6h and the effect was sustained until 24 th h with 400mg/kg. In subacute study, antihyperglycaemic effect was observed on 21st day. In PPSBPE treated mice the body weight was not reduced in contrast to that in vehicle group. In OGTT, increased glucose utilization was observed., Conclusions: It is concluded that PPSB-PEE but not PPSB-AQE showed antihyperglycaemic activity.

Insulin resistance and subsequent insulin secretory defect are two main features of type 2 diabetes and associated metabolic disorders. The animal models of type 2 diabetes are very complex and are as heterogeneous as the disease. We have evaluated the effect of various antidiabetic and lipid lowering agents (fenofibrate, rosiglitazone, glimepiride, metformin and simvastatin) on the metabolic abnormalities induced by combining a high-fat diet and multiple low-dose streptozocin (MLDS) in mice. Male Swiss albino mice were orally treated with the above agents and fed with a diet containing high fat for 28 days. On day 15 the animals were injected intraperitoneally with low-dose streptozocin (40 mg kg(-1)), which was administered for five consecutive days. At the end of the 28-day treatment plasma metabolic parameters (glucose, triglyceride and immunoreactive insulin) were estimated. The antidiabetic and hypolipidaemic agents exhibited differential effects on these metabolic parameters. With the exception of fenofibrate all these agents reduced the plasma glucose levels, and the effects of metformin and rosiglitazone on glucose were found to be statistically significant. Although the effect of the test drugs on cholesterol was modest, a significant decrease in triglyceride levels was observed with sub-chronic treatment with these agents. Interestingly, glimepiride mildly elevated the insulin levels while the other antidiabetics and hypolipidaemics reduced the insulin levels, with metformin and rosiglitazone exhibiting statistically significant effects on insulin. To our knowledge this is the first report on the effect of various peroxisome proliferator-activated receptor modulators and newer antidiabetics on the metabolic effects induced by the combined high-fat diet and MLDS model of type 2 diabetes in Swiss albino mice. The results suggested the complexity of the hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia induced by the high-fat diet and MLDS mouse model, and their correction by various antidiabetics and antihyperlipidaemics may have involved diverse mechanisms.

Abnormalities in glucose and lipid regulation have been reported in schizophrenia during antipsychotic medications. The objectives of the present study were to evaluate the effect of various peroxisome proliferator-activated receptor modulators viz. glimepiride, rosiglitazone and fenofibrate on chlorpromazine, clozapine and ziprasidone induced hyperglycemia and hyperlipidemia in mice. Male Swiss albino mice were orally treated with chlorpromazine, clozapine and ziprasidone concurrently with the antidiabetic medications for 7 days. Plasma glucose, insulin and triglyceride levels were determined at the end of the study. Chlorpromazine and clozapine elevated the glucose and triglyceride levels in normal mice, with no effect on insulin but ziprasidone increased the basal triglyceride and insulin levels and did not have any effect on glucose. Glimepiride and rosiglitazone showed beneficial glucose and triglyceride lowering effects in chlorpromazine and clozapine animals and no effect on insulin levels. Fenofibrate significantly reduced the glucose levels only in animals treated with clozapine, and exhibited significant reduction of triglyceride levels in chlorpromazine, clozapine and ziprasidone treated animals. All three antidiabetic/hypolipidemic agents lowered triglyceride and insulin levels in ziprasidone treated animals. The results of the present studies suggest that hyperglycemia, hyperinsulinemia and hypertriglyceridemia induced by various antipsychotics may involve diverse mechanisms.